MCB 3210/5210 Molecular Endocrinology (I)

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MCB 3210/5210 Molecular Endocrinology (I)

• Instructor
• Propfessors Thomas T. Chen, Office TLS Rm 413A
  Tel [phone] E-mail Thomas.Chen_at_uconn.edu
• Professor Jianjun Sun, Office PBB 117A Tel
  860-486-5481 E-mail Jianjun.Sun_at_uconn.edu
• Office hour Tue 100-300 p.m. or by appointment
• Class Meeting Time Tue and Thu 1100 a.m. to
  1215 p.m. in TLS Rm 263
• Text Book
• Recommended textbook Vertebrate Endocrinology
  5th ed. by David O. Norris
• Some original papers will be assigned in class
  for additional reading
• Course Grade
• For MCB 3210 average of two exams (Mid-term and
  Final)
• For MCB 5210 average of two exams (70) one in
  class presentation and a 20-page essay on the
  same topic of presentation (30)

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MCB 3210/5210 Molecular Endocrinology (II)

• Two Lecture Exams
• Exam I Tue, October 14th
• Exam II During the final exam week (to be
  announced)
• Duration of lecture per period 75 min
• Exam questions will consist of short or long
  answers and problem solving questions. Materials
  will be taken from lecture materials and the
  assigned reading materials in the textbook and
  original research papers
• Lecture materials will be posted on the website.
  Each student is responsible for printing out the
  materials from the website and bring to class for
  the lectures
• Class website http//www.sp.uconn.edu/ttc02001/M
  CB3210-5210/
• An extra credit essay paper (20 pages,
  double-space)

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I. Introduction
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Molecular Endocrinology

• Molecular Endocrinology Studies of structures,
  synthesis and actions of hormones (bioregulators)
  at cellular and molecular levels
• Definition of hormone
• Classic definition Hormones are chemical
  substances produced by specialized tissues
  (endocrine glands) and secreted into the blood
  stream, where they are carried to target organs
• Broader definition Hormone are chemicals,
  non-nutrients, intracellular messengers that are
  effective at micromolar concentrations or less.
  In other words hormones are chemical substances
  that carry information between two or more cell
  types. They are also called as bioregulators
• Discrepancies between the classic and the broader
  definitions
• Specialized tissue for hormone synthesis (vs.
  multiple tissues)
• Blood for hormone distribution (vs. blood,
  intercellular fluid)
• A separate organ for hormone action (vs. multiple
  target tissues)

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Origins of Chemical Communication

1. Early cells living in the primordial seas
   developed receptors for recognition of
   water-soluble toxins, nutrients and internal
   receptors for lipids that could readily pass
   through the membrane. Some of these receptors
   transferred these molecules into the cell for
   metabolism or detoxification
2. Besides accumulating molecules intracellularly,
   early cells also released special molecules into
   the environment that were detected via receptors
   on other cells and served as a mechanism for
   cell-to-cell communication. Various features of
   these ancient mechanisms for accumulation,
   detoxification, metabolism, and chemical
   communication have persisted in one form or
   another in all living cells to this day

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Categoreies of Bioregulators

• Chemical communication involves
• Neurocrines, including neurotransmitters or
  neuromodulators
• Neurohormones
• Hormones
• Autocrine/paracrine regulators
• Ectohormones (semiochemicals)
• The liver and kidney serve as major sites for the
  metabolism and excretion of bioregulators.

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Chemical Bioregulation

• Bioregulation is defined as secretion of
• The endocrine system
• The nervous system
• The immune system
• Virtually all cells in the body that use
  chemicals to communicate with one another
• Bioregulators

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Types of Regulators
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Some Mammalian Neurocrine Regulators
The separation of neural and endocrine systems
have become more blurred when it was learned that
some established hormones also were produced
within the nervous system where they function as
neurotransmitters or neuro-modulators
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Some Important Terms

• Endocrine glands
• Hormones
• Receptors
• Hormone-receptor complex
• Bioregulation, bioregulators
• Environmental endocrinology
• Endocrine disruption, endocrine disrupting
  chemicals (EDCs), endocrine active chemicals
  (EACs)
• Diethylstilbestrol (DES), DDT, polychlorinated
  biphenyls (PCBs) (examples of EDCs) are known
  endocrine disruptors

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Some Terms

• Cytocrine local hormones including growth
  factors, mitogenic regulators, embryonic
  tissue-inducing substances, secretogogues
  (secretion-enhancing factors), inhibitors and
  immune regulators. These factors can act as
  autocrines or paracrines
• Intracrines Chemical messengers (secondary
  messengers or transcription factors) that govern
  intracellular events
• Endocrines Hormones
• Ectohormones (semiochemicals) Chemical
  messengers secreted from one organism into the
  environment that affect the physiology or
  behavior of another organism. Example
  pheromones (primer pheromone, releaser
  pheromone), Allelomes (allomones and kairmones)

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Chemical Nature of Bioregulators

• Peptide and protein hormones (most abundant)
  thyrotropin releasing hormone, GnRH, GH, PRL,
  insulin etc.
• Amino acid derivatives thyroid hormone,
  epinephrine
• Steriod hormones testostrone, estrogen, cotisone
  etc.
• Lipids prostaglandin, retinoic acid etc.
• Nucleotides cAMP, cytokinins, 1-methylalanine
  etc.
• Oligosaccharides a-1,4-oligogalacturonide
• Gases CO, ethylene etc

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Structural Diversity of Hormones

• A. Thyrotropin releasing hormone
• B. Epinephrine
• C. Cortisol
• D. Prostaglandin
• E. Plated activating factor
• F. Zeatin (a cytokinin)
• G. a-1,4-oligogalacturonide (an elicitor)
• H. ethylene

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Functional Conceptualization of the Endocrine
System
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Organization of Bioregulator Systems

• Neuroendocrine system Brain (hypothalomus) and
  pituitary gland (producing tropic hormons and
  other hormones)
• Classical endocrine glands thyroid gland,
  adrenal glands, gonads, and liver
• Independent endocrine glands parathyroid glands,
  thymus, endocrine pancreas, organs of the
  gastrointestinal tract, pineal gland and the
  kidney
• Tropic hormones Hormones secreted by
  hypothalamus that regulate the secretion of
  peptide or protein hormone from pituitary glands,
  thyroid glands, adrenal cortex, gonads and liver
• Table 1-3 in the textbook and the following few
  slides list many of these hormones. Please read.

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Major Mammalian Endocrine Secretions (I)

• Hypothalamus
• producing hypothalamus releasing neurohormones
  such as TRH, GnRH, CRH, GHRH, GH-RIH, PRIH, PRH,
  MRIH, MRH
• Producing other neurohormones such as AVP, OXY,
  Endophines/enkephalins
• Anterior pituitary
• Producing glycoprotein tropic hormones such as
  TSH, LH (leuteinizing hyormone), and FSH
• Producing nonglycoprotein tropic hormone such as
  GH, PRL, ATCH, and melanotropin (MSH)
• Thyroid gland
• Producing thyroid hormones (T3 and T4) and
  calcitonin
• Gonads
• Ovary producing estrogens, progestrone and
  inhibin
• Testis producing testostrone and other
  androgens,a d inhibin

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Major Mammalian Endocrine Secretions (II)

• Adrenal glands
• Adrenal cortex producing aldosterone and
  corticosterone/ cortisol
• Adrenal mediulli producing epinephrine/norepineph
  ine
• Parathyroid gland
• Producing PTH
• Endocrine pancreas
• Producing insulin, glucogon, pancreatic
  polypeptide GH-RIH
• Liver
• IGF-I and IGF-II
• Adipose tissue
• Producing leptin
• Kidney
• Producing erythropoietin, renin, and
  1,25-dihydrocholecalciferol

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Major Mammalian Endocrine Secretions (III)

• Gastrointestinal system
• Stomach producing gastrin and ghrelin
• Small intestine producing secretin,
  cholecystokinin, gastrin-rteleasing peptide,
  gastric inhibitory peptide, motilin, somatostatin
  and vasoactive intestinal peptide
• Pineal gland
• producing melatonin
• Immune system
• Thymus producing thymosins
• Macrophages/lymphocytes producing interleukin 1
  and lnterleukin 2

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Morphological Features of Bioregulator Secreting
Cells
Steroid secreting cells
Growth hormone secreting cells
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Organization of Endocrine Cells
(A) Cells secreting growth hormone (orange) and
gonadotropins (blue) in a pituitary gland (B)
Islet of insulin secreting cells (arrow) embedded
within the darker stained exocrine pancreas (C)
Follicles from a thyroid gland showing a thin
epithelium and pink colloid filling the lumen of
the follicle. (D) Isolated clusters of
testosterone secreting interstitial cells (arrow)
located between seminiferous tubules in a testis.
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Homeostasis

• Defined by Walter B. Cannon Balanced
  physiological systems operating in the organism
  to maintain a dynamic equilibrium (a relatively
  constant steady state) maintained within certain
  tolerable limits
• This concept was originally used to describe the
  maintenance of blood parameters such as osmotic
  pressure, volume, hydrostatic pressure and levels
  of various simple chemicals Ca, Na and glucose
• It can be expanded to include all manner of
  physiological bioregulation at the level of
  organism and at the levels of molecular and
  cellular levels

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Hormonal Control Systems

• Negative feedback control Rising levels of a
  hormone shuts down the production of the hormone
  so that its level can be maintained. Example
  cortisol inhibits hypothalamus to produce CRF to
  control adrenal cortex to produce cortisol
• Positive feedback control Rising hormone levels
  stimulates further production of the hormone.
  Example production of oxytocin near parturition
• Cycle-dependent feedback control Nagative and
  positive controls function together. Example
  estrogen negative feedback control hypothalamus
  to produce more estrogen in nonmidcycle, but at
  midcycle, estrogen positive regulate hypothalamus
  to produce more estrogen to induce a surge of
  luteinizing hormone leading to ovulation

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Feedback Regulation of Hormone Secretion

1. Negative Feedback
2. Positive Feedback
3. Cycle-dependent Feedback

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Life History of a Hormone
Liver and kidney are major sites of hormone
metabolism and excretion
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Endocrine Disruption of Homeostasis

• The homeostasis in an organism can be profoundly
  affected by endocrine imbalances
• Some examples of endocrine disorders acromegaly
  goiter, type I and type II diabetes, rickets,
  Turners syndrome, polycystic ovary syndrome etc.
• In recent years, endocrinologists have focused
  on the presence of chemicals in the environment
  that can potentially disrupt endocrine functions.
  These chemicals are called as Endocrine
  Disrupting Compounds (EDCs).
• EDCs can function directly to disrupt the
  activities of endocrine glands or mimics the
  activities of hormones
• Examples of EDCs
• Insecticides such as DDT or metabolites of DDT
• Herbicides such as atrazine, glyophoste
• Fungicides such as vinclozolin
• Industril or mining byproducts such as heavy
  metals, dioxins and PCBs
• Estrogenic or anti-androgenic compounds
• For details, see Table 1-6 in the textbook